Lactic Acidosis in the Setting of Antiretroviral Therapy for the Acquired Immunodeficiency Syndrome

Abstract

Type B lactic acidosis, a rare but often fatal disorder, has been reported in 21 AIDS patients on antiretroviral therapy (ART). We present an AIDS patient with severe and prolonged lactic acidosis on stavudine and lamivudine. The lactic acidosis occurred in the absence of mitochondrial myopathy, hepatomegaly, or liver failure. This is the second report of lactic acidosis in a patient on stavudine and lamivudine. This patient recovered after aggressive supportive therapy including intravenous alkali and fluid administration as well as continuous venovenous hemodiafiltration. A single dose of dichloroacetate (DCA) was associated with a decrease in the serum lactate level by 20%, which persisted for more than 24 h. Seventeen months after recovery, the patient was rechallenged with ART without recurrence of lactic acidosis. We review and summarize all reported cases of patients with ART-associated lactic acidosis reported in the English literature.

Highly Active Antiretroviral Therapy and the Kidney

“…NRTI have been associated with development of disturbances in lactic acid homeostasis with presentations that range from asymptomatic chronic hyperlactatemia to acute, life-threatening lactic acidosis. Lactic acidosis was first described with didanosine and, even more common, zidovudine (105)(106)(107). Many of these patients also had massive hepatic steatosis and liver failure, and most died within a few days or weeks.…”

“…Some patients tolerate resumption of NRTI therapy but require close monitoring (110). Intermittent hemodialysis or continuous renal replacement therapy and bicarbonate supplementation may be indicated in severe cases (107,123). Various therapies, including thiamine, l-carnitine, coenzyme Q 10 , and riboflavin, among others, have been tried but are of unproved efficacy (110 -112,124).…”

Severe Lactic Acidosis in Association with Reverse Transcriptase Inhibitors with Potential Response to L-Carnitine in a Pediatric HIV-Positive Patient

“…[1][2][3] Despite being incompletely understood, this complication appears to result from mitochondrial failure related to the inhibition of mitochondrial DNA polymerase-g. [2][3][4][5] Although frequently fatal, there have been reports of significant improvement after interventions such as administration of riboflavin, carnitine, thiamine, coenzyme Q, dichloroacetate, and the institution of hemofiltration. [4][5][6][7] We present a case of life-threatening lactic acidosis in a child receiving d4T, ddl, and nevirapine, which responded noticeably following treatment with carnitine.…”

Mitochondrial and Metabolic Effects of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in Mice Receiving One of Five Single- and Three Dual-NRTI Treatments

“…However, NRTIs can induce side effects of differing severity and frequency (6,12,26). Liver failure, lactic acidosis, or pancreatitis may be severe and sometimes fatal, but these occur in only a few patients (7,13,17,48). Lipodystrophy and hyperlactatemia are less severe but much more frequent (14,35).…”